Concise Review: Modeling Neurodegenerative Diseases with Human Pluripotent Stem Cell-Derived Microglia

Stem Cells
Walther Haenseler, Lawrence Rajendran

Abstract

Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)-derived microglia have recently been developed and provide unlimited access to patient-derived material. In this present study, we give an overview of iPSC-derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microgli...Continue Reading

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Citations

Dec 4, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Swati NaphadeLisa M Ellerby
Jan 12, 2020·Glia·Jonathan Hasselmann, Mathew Blurton-Jones
Jul 25, 2019·Translational Neurodegeneration·Sherida de Leeuw, Christian Tackenberg
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Nov 7, 2020·Molecular Psychiatry·Orly ReinerArpan Parichha
Dec 29, 2020·Frontiers in Immunology·Anne HedegaardSally A Cowley
Feb 13, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jing WuJingfa Zhang
Jan 12, 2021·Nature Protocols·Nicola FattorelliRenzo Mancuso
Mar 27, 2021·Current Opinion in Gastroenterology·Edgar N TafalengAlejandro Soto-Gutierrez
Dec 15, 2020·Progress in Neurobiology·Hannah FranklinRickie Patani
Apr 13, 2021·Frontiers in Cell and Developmental Biology·Samantha N Lanjewar, Steven A Sloan
Jul 23, 2021·The Journal of Experimental Medicine·Yun Chen, Marco Colonna
Aug 15, 2021·Neuron·Anaelle Aurelie DumasMarco Prinz

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Methods Mentioned

BETA
gene knockout
dissection

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